The crude resin obtained from the flowering tops of female plants of several varieties of Cannabis sativa L. has been known for its psychotomimetic activity since antiquity. Common names assigned to some of these varieties include marijuana, hashish, charas, dagga, and bhang.
With the advent of advanced analytical techniques, it has been determined that the resin contains a variety of ingredients varying in molecular configuration, with both the components and their proportions varying from one source to the next. In general, the active compounds have the following formula where R is hydrogen or alkyl containing from one to ten carbon atoms. They are useful as psychotomimetic agents, sedatives, and analgesics. ##STR1##
Extensive studies have led to the identification of a single component as the one primarily responsible for the psychotomimetic activity. Although its complicated ring structure gives rise to differing nomenclature depending upon the numbering system used, the active component is most commonly referred to as (-)-6a,10a-trans-1-hydroxy-3-n-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydr odibenzo[b,d]pyran, in which R in the formula above is n-pentyl and occupies the meta position with respect to the hydroxyl group. This components is also known by the simplified names "trans-.DELTA..sup.9 -tetrahydrocannabinol" and "trans-.DELTA..sup.9 -THC."
Following the identification of this ingredient, a variety of synthetic preparation methods were developed, in order to eliminate the need to extract the material from natural sources. A survey of these techniques can be found in the comprehensive article by Mechoulam et al., entitled "Recent Advances in the Chemistry and Biochemistry of Cannabis," Chemical Reviews, 76 (1), pp. 75-112 (1976). Two notable techniques are those described by Petrzilka et al. in Helv. Chim. Acta, 52, 1102 (1969), and by Razdan et al. in J. Am. Chem. Soc., 96, 5860 (1974).
In addition to its psychotomimetic properties, the active ingredient has also been found to be a beneficial adjunct to cancer treatment in view of its ability to suppress the unpleasant side-effects which accompany chemotherapy. For this reason as well as its psychotomimetic activity, there is a serious need for comprehensive testing of the material in order to determine in full detail its pharmacological effects. For reliable and reproducible results, test samples of the material must be obtained in a highly pure state. Unfortunately, synthetic procedures tend to produce a mixture containing a broad variety of geometric isomers, optical isomers, intermediates, unreacted starting materials, and products of assorted side-reactions. Many of these can be separated from the active component by conventional separation techniques. A certain number, however, particularly the isomers, are extremely difficult to remove.
The only process developed to date which has been effective in supplying a product of sufficient purity is a low pressure liquid chromatography process. This process has several disadvantages. First, there are practical limitations on the scale-up of liquid chromotography equipment in terms of the diameter and length of the columns due to the need to avoid certain undesirable effects. Such limitations, together with considerations of packing efficiencies and absorbent weights, impose a severe limitation on the column through-put rate. As a result, a practical liquid chromatography system requires a tank farm containing several columns. Second, a solvent recovery system is necessary in order to separate out the product and recycle the solvent, entailing extensive processing equipment and the frequent attention of plant operators. This adds greatly to the expense. Third, the large number of vessels and transfer lines tends to increase the danger of handling losses and potential theft. A serious need thus exists for a simplified purification system with a lower capital investment, a lesser need for operator attention, a higher through-put rate, and better product accountability.